The ultimate goal of this program is to develop new approaches to selective protection of gastrointestinal tract and bone marrow from radiotherapy side effects, thus improving therapy efficacy and life quality of patients. CBLB502 is a proprietary radiation countermeasure which is currently in Phase I trials for biodefense indication. Single injection of CBLB502 reduces radiation damage to the bone marrow and GI tract of mice and non-human primates in the context of high dose total body irradiation. This protection is selective for normal cells and does not affect radiosensitivity of experimental solid tumors. We hypothesize that CBLB502 treatment can also protect normal tissues during radiation therapy (which is usually delivered locally in multiple fractions). Current proposal is devoted to testing the feasibility of this approach in three mouse models of radiation therapy and normal tissue injury: head and neck, small intestine and bone marrow. In addition, the lack of protection of tumor cells of hematopoietic origin by CBL8502 will be assessed in bone marrow transplantation model. The success of this program will enable further studies needed to accumulate the evidence necessary to advance CBL8502 10 inclusion in clinical trials of cancer therapy.